ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.4077-10C>T

gnomAD frequency: 0.00233  dbSNP: rs145310008
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000123854 SCV000167197 benign not specified 2014-02-26 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000227864 SCV000283147 benign Bloom syndrome 2021-12-17 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV000227864 SCV000394434 likely benign Bloom syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Eurofins NTD LLC (GA) RCV000123854 SCV000855793 likely benign not specified 2017-08-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000123854 SCV000918646 benign not specified 2019-12-23 criteria provided, single submitter clinical testing Variant summary: BLM c.4077-10C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00057 in 250972 control chromosomes, predominantly at a frequency of 0.0079 within the African or African-American subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 2.2 fold of the estimated maximal expected allele frequency for a pathogenic variant in BLM causing Bloom Syndrome phenotype (0.0035), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.4077-10C>T in individuals affected with Bloom Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (benign, n=1; likely benign, n=1, VUS, n=1). Based on the evidence outlined above, the variant was classified as benign.
Mendelics RCV000227864 SCV001139717 likely benign Bloom syndrome 2019-05-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000123854 SCV002046909 benign not specified 2021-04-29 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000123854 SCV002071186 likely benign not specified 2020-10-16 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV002257453 SCV002533040 likely benign Hereditary cancer-predisposing syndrome 2021-03-14 criteria provided, single submitter curation
Natera, Inc. RCV000227864 SCV002090649 likely benign Bloom syndrome 2017-08-09 no assertion criteria provided clinical testing

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